Featured Research

from universities, journals, and other organizations

Rare gene mutation sheds light on protein's role in brain development

Date:

October 16, 2013

Source:

Duke Medicine

Summary:

Though worlds apart, four unrelated families have been united in a medical mystery over the source of a rare inherited disorder that results in their children being born with abnormal brain growth and severe functional impairments.

Share This

Though worlds apart, four unrelated families have been united in a medical mystery over the source of a rare inherited disorder that results in their children being born with abnormal brain growth and severe functional impairments.

Related Articles

An international team of scientists, led by genetic researchers at Duke Medicine, has solved the case by identifying a recessive gene mutation that reduces the abundance of a certain protein that previously had not been known to affect brain development.

The gene mutation causes a defect in the body's synthesis of a nutrient called asparagine, which is found in meat, dairy and nuts, among other foods. Long considered a "non-essential" amino acid, asparagine synthesis may actually be crucial for normal brain development and function.

The findings appear in the Oct. 16, 2013, issue of the journal Neuron.

"This non-essential amino acid has different levels inside and outside the central nervous system, and it may be that in the central nervous system, it plays a critical role," said lead author David B. Goldstein, Ph.D., director of the Center for Human Genome Variation and professor of Molecular Genetics & Microbiology and professor of biology at Duke University School of Medicine. "What is exciting about this is if we can work out how it functions, a treatment might be asparagine supplementation in the diet."

Goldstein said the work on the rare disorder was launched after two separate families in Israel, both of Iranian Jewish ancestry, had children with similar impairments -- small head circumference that grows progressively worse, accompanied by profound developmental delays and seizures.

Deducting that the families' ethnic heritage might help focus the gene quest, Goldstein and colleagues looked for gene variants that were shared by the two affected children from one of the families, but were uncommon in the general population. Of 72 such variants, three were absent in the larger population.

Of those three variants, one was also present in the child of the other family from Israel. This mutation was located in the asparagine synthetase gene, or ASNS, which controls the production of the metabolite asparagine from other amino acids.

Meanwhile, two other families -- both in Canada -- had children who were born with similar problems, and scientists there conducted analyses that pointed to mutations in the same ASNS genes.

In combining the cases, the researchers discovered that each of the parents in these four families shared a rare recessive trait that, by chance, combined to result in a newly identified disorder in their children. More cases are likely to come to light now that the gene mutation has been identified.

Goldstein said other similar deficiencies in amino acids synthesization -- all causing neurological problems -- have recently been identified. These conditions have shown improvement with the use of dietary supplements, suggesting that the impairments caused by the ASNS mutation might benefit from asparagine supplementation.

"An emerging theme is that with these 'non-essential' amino acids, their metabolism does matter," Goldstein said. "This metabolic pathway is important, and it may be that the amount of asparagine is the key, or a buildup of toxin in that pathway caused by the mutation."

Goldstein said future research in mice bred to have a similar disorder could prove enlightening. Already, he said, experiments have shown that mice with ASNS mutations have a less severe form of the disorder, perhaps because they have higher levels of asparagine in their bloodstream. That insight, he said, adds hope to the prospect that dietary supplementation might diminish the impact of the mutation.

"We can now use these mice to investigate the appropriate quantities and timing of the asparagine dietary supplementation," said lead author Elizabeth Ruzzo. "Given that this is a developmental disorder it is possible that adjusting the mother's diet before she is even pregnant will be most effective."

Story Source:

The above story is based on materials provided by Duke Medicine. Note: Materials may be edited for content and length.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Feb. 4, 2013 — Mutations which affect the gene ASXL3 cause a novel syndrome similar to Bohring-Opitz syndrome, finds a a new study. This molecular definition distinguishes these children from those with ... full story

Jan. 22, 2013 — Researchers have identified a rare gene mutation in a single family with a high rate of schizophrenia, adding to evidence that abnormal genes play a role in the development of the ... full story

Sep. 8, 2011 — Narcolepsy is a rare disorder characterized by an excessive urge to sleep at inappropriate times and places. Narcoleptics are also often subject to "cataplexy," a sudden muscle weakness ... full story

Apr. 26, 2010 — Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare genetic disorder that was identified in an Old Order Mennonite pediatric population. It is characterized by abnormal ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.